赵慧强,陈晖,李东宝,李虹伟,王守力,韩雅玲

• 1:首都医科大学附属北京友谊医院心血管病中心心内科
• 2:沈阳军区总医院全军心血管病研究所心内科

摘要(Abstract)：

目的探讨冠状动脉闭塞后不同时期心肌内小动脉和微动脉的重构情况。方法 56头中国小型猪,采用置入铜丝支架的方法制作冠状动脉慢性完全闭塞模型。分别在术后1周(A组,5头)、2周(B组,6头)、4周(C组,9头)、3个月(D组,9头)、6个月(E组,10头)复查超声心动图和冠状动脉造影(CAG)后处死。取梗死区域的冬眠心肌和坏死区域组织分别做HE、Masson染色。采用图像分析系统测量计算管腔面积/血管总面积(LA/EELA),管壁面积/管腔面积(WA/LA);计算梗死区域内小动脉和微动脉的管壁胶原面积。采用透射电镜检查观察小动脉和微动脉管壁成分和血管平滑肌细胞的结构改变。结果与对照组比较,在冬眠心肌和坏死区域内B组、C组、D组和E组的小动脉和微动脉均出现了明显的血管重构,表现为WA/LA增加(P<0.05,F=18.07,F=22.35),LA/EELA减小(P<0.05,F=8.84,F=10.12)。Masson染色显示,E组、D组、C组(P<0.05,F=32.03,F=38.21)的小动脉和微动脉管壁的胶原面积明显高于对照组及A、B组。透射电镜发现B、C、D和E组小动脉和微动脉管壁中合成表型的血管平滑肌细胞明显增多。结论冠状动脉闭塞一段时间后冬眠心肌和坏死区域内的小动脉和微动脉可发生血管重构,主要改变为内膜增生导致的管壁增厚和管腔狭窄,而且,随冠状动脉闭塞时间延长,血管壁逐渐发生纤维化。小动脉和微动脉的重构可能会减少冬眠心肌的血液供应,使冬眠心肌数量减少;在血运重建后可能会减少冬眠心肌的前向供血,影响冬眠心肌和心功能的恢复。

关键词(KeyWords)： 疾病模型,动物;冠状动脉闭塞;心室重构

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 赵慧强,陈晖,李东宝,李虹伟,王守力,韩雅玲

参考文献(References)：

• [1]Claeys MJ,Vrints CJ,Bosmans J,et al.Coronary flow reserve during coronary angioplasty in patients with recent myocardial infarction:relation to stenosis and myocardial viability.J Am Coll Cardiol,1996,28:1712-1719.
• [2]Ragosta M,Powers ER,Samady H,et al.Relationship between extent of residual myocardial viability and coronary flow reserve in patients with recent myocar-dial infarction.Am Heart J,2001,141:456-462.
• [3]Crea F,Davies G,Crake T,et al.Variability of coronary blood flow reserve assessed by Doppler catheter after successful thrombolysis in patients with acute myocar-dial infarction.Am Heart J,1993,125:1547-1552.
• [4]Kawamoto T,Yoshida K,Akasaka T,et al.Can coronary blood flow velocity pattern after primary percuta-neous transluminal coronary angioplasty[correction of angiography]predict recovery of regional left ventricular function in patients withacute myocardial infarction?Circulation,1999,100:339-345.
• [5]Lepper W,Hoffmann R,Kamp O,et al.Assessment of myocardial reperfusion by intravenous myocar-dial contrast echocardiography and coronary flow reserve after primary percutaneous transluminal coronary angioplasty[correction of angiography]in patients with acute myocardial infarction.Circulation,2000,101:2368-2374.
• [6]Feldman LJ,Himbert D,Juliard JM,et al.Reperfusion syndrome:Relationship of coronary blood flow reserve to left ventricular function and infarct size.J Am Coll Cardiol,2000,35:1162-1169.
• [7]Wakatsuki T,Nakamura M,Tsunoda T,et al.Coronary flow velocity immediately after primary coronary stenting as a predictor of ventricular wall motion recovery in acute myocardial infarction.J Am Coll Cardiol,2000,35:1835-1841.
• [8]Ragosta M,Camarano G,Kaul S,et al.Microvascular integrity indicates myocellular viability in patients with recent myocardial infarction:New insights using myocardial contrast echocardiography.Circulation,1994,89:2562-2569.
• [9]Vernon S,Kaul S,Powers ER,et al.Myocardial viability in patients with chronic coronary artery disease and previous myocardial infarction:Comparison of myocar-dial contrast echocardiography and myocardial perfusion scintigra-phy.Am Heart J,1997,134:835-840.
• [10]Teiger E,Garot J,Aptecar E,et al.Coronary blood flow reserve and wall motion recovery in patients undergoing angioplasty for myocardial infarction.Eur Heart J,1999,20:285-292.
• [11]Uren NG,Crake T,Lefroy DC,et al.Reduced coronary vasodilator function in infarcted and normal myocardium after myocardial infarction.N Engl J Med,1994;331:222-227.
• [12]Werner GS,Ferrari M,Richartz BM,et al.Microvascular dysfunction in chronic total coronary occlusions.Circulation,2001,104:1129-1134.
• [13]Werner GS,Emig U,Bahrmann P,et al.Recovery of impaired microvascular function in collateral dependent myocardium after recanalisation of a chronic total coronary occlusion.Heart,2004,90:1303-1309.
• [14]Thengchaisri N,Shipley R,Ren Y,et al.Exercise trainingrestores coronary arteriolar dilation to NOS activation distal to coronary artery occlusion:role of hydrogen peroxide.Arterioscler Thromb Vasc Biol,2007,27:791-798.
• [15]Griffin KL,Woodman CR,Price EM,et al.Endothelium-mediated relaxation of porcine collateral-dependent arterioles is improved by exercise training.Circulation,2001,104:1393-1398.
• [16]Rapps JA,Sturek M,Jones AW,et al.Altered reactivity of coronary arteries located distal to a chronic coronary occlusion.Am J Physiol,1997,273:H1879-H1887.
• [17]Koch KT,Schotborgh CE,Tijssen JG,et al.Time course of microvascular resistance of the infarct and noninfarct coronary artery following an anterior wall acute myocardial infarction.Am J Cardiol,2006,97:1131-1136.
• [18]Neumann FJ,Kosa I,Dickfeld T,et al.Recovery of myocardial perfusion in acute myocardial infarc-tion after successful balloon angioplasty and stent placement in the infarct-related coronary artery.J Am Coll Cardiol,1997,30:1270-1276.
• [19]Hong H,Aksenov S,Guan X,et al.Remodeling of small intramyocardial cornory arteries distal to a severe epicardial cornory artery stenosis.Arterioscler Thromb Vasc Biol,2002,22:2059-2065.
• [20]Sorop O,Merkus D,de Beer VJ,et al.Functional and structural adaptations of coronary microvessels distal to a chronic coronary artery stenosis.Circ Res,2008,102:795-803.
• [21]赵慧强,韩雅玲,王守力,等.中国小型猪冠状动脉慢性完全闭塞病变模型的建立.中国介入心脏病学杂志,2011,19:306-312。
• [22]Silver AE,Vita JA.Shear-stress-mediated arterial remodeling in atherosclerosis:too much of a good thing?Circulation,2006,113:2787-2789.
• [23]Chiu JJ,Chen LJ,Chen CN,et al.A model for studying the effect of shear stress on interactions between vascular endothelial cells and smooth muscle cells.J Biomech,2004,37:531-539.
• [24]Qiu Y,Tarbell JM.Interaction between wall shear stress and circumferential strain affects endothelial cell biochemical production.J Vasc Res,2000,37:147-157.
• [25]Nerem RM,Harrison DG,Taylor WR,et al.Hemodynamics and vascular endothelial biology.J Cardiovasc Pharmacol,1993,21:S6-S10.
• [26]Ueba H,Kawakami M,Yaginuma T.Shear stress as an inhibitor of vascular smooth muscle cell proliferation.Role of transforming growth factor beta1and tissue-type plasminogen activator.Arterioscler Thromb Vasc Biol,1997,17:1512-1516.
• [27]Pistea A,Bakker EN,Spaan JA,et al.Flow inhibits inward remodeling in cannulated porcine small coronary arteries.Am J Physiol Heart Circ Physiol,2005,289:H2632-H2640.
• [28]Beltrami CA,Finato N,Rocco M,et al.Structural basis of end-stage failure in ischemic cardiomyopathy in humans.Circulation,1994,89:151-163.
• [29]Haas F,Augustin N,Holper K,et al.Time course and extent of improvement of dysfunctioning myocardium in patients with coronary artery disease and severely depressed left ventricular function after revascularization:correlation with positron emission tomographic findings.J Am Coll Cardiol,2000,36:1927-1934.
• [30]Chen C,Liu J,Hua D,et al.Impact of delayed reperfusion of myocardial hibernation on myocardial ultrastructure and function and their recoveries after reperfusion in a pig model of myocardial hibernation.Cardiovasc Pathol,2000,9:67-84.
• [31]Elsasser A,Decker E,Kostin S,et al.A self-perpetuating vicious cycle of tissue damage in human hibernating myocardium.Mol Cell Biochem,2000,213:17-28.